The proposed work is ultimately directed to elucidating the biophysical basis of nervous dysfunction in demyelinating disease. Changes will be sought in the pattern of distribution of sodium channels and sodium pumps in the nerve membrane during the processes of normal myelination (in the newborn animal) and of demyelination, produced experimentally in a number of ways. A variety of electrophysiological and pharmacological techniques will be used. Voltage-clamp experiments will be done to determine the Hodgkin-Huxley parameters for mammalian myelinated nerve. Gating currents will also be measured. The electrophysiological consequences of myelination will be examined experimentally.